β-arrestins mediates ERK activation in clathrin-coated pits (DeFea et al., 2000). β-arrestins act as a scaffolds that bind C-Raf, MEK, and ERK and direct signaling to the cytosol preventing ERK translocation to the nucleus (DeWire et al., 2007; Shenoy and Lefkowitz, 2011) Dysregulation of β-arrestins expression, localization, or phosphorylation is associated with more aggressive cancer phenotypes and poorer prognosis in breast, prostate, lung, brain, and hematological tumors (Sobolesky and Moussa, 2013). The gene discussed is RAF1; the disease is cancer.